Premium
Rotenone partially reverses decreased BK Ca currents in cerebral artery smooth muscle cells from streptozotocin‐induced diabetic mice
Author(s) -
Dong Ling,
Xie ManJiang,
Zhang Peng,
Ji LeLe,
Liu WenChong,
Dong MingQing,
Gao Feng
Publication year - 2009
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2009.05222.x
Subject(s) - rotenone , streptozotocin , endocrinology , medicine , vascular smooth muscle , diabetes mellitus , vasodilation , vasoconstriction , chemistry , mitochondrion , smooth muscle , biochemistry
Summary1 Reactive oxygen species (ROS) cause vascular complications and impair vasodilation in diabetes mellitus. Large‐conductance Ca 2+ ‐activated potassium channels (BK Ca ) modulate vascular tone and play an important negative feedback role in vasoconstriction. In the present study, we tested the hypothesis that ROS regulate the function of BK Ca in diabetic cerebral artery smooth muscle cells. 2 Diabetes was induced in male BALB/c mice by injection of streptozotocin (STZ; 180 mg/kg, i.p., dissolved in sterile saline). Control and diabetic mice were treated with 12.7 µmol/L rotenone, an inhibitor of the mitochondrial electron transport chain complex I, or placebo every other day for 5 weeks. The whole‐cell patch clamp‐technique and functional vasomotor methods were used to record BK Ca currents and myogenic tone of cerebral artery smooth muscle cells. 3 In the diabetic group, there was a significant decrease in spontaneous transient outward currents in cerebral artery smooth muscle cells compared with control. Although the currents were only moderately increased in rotenone‐treated diabetic mice, they remained significantly lower than in the control group. Furthermore, the macroscopic BK Ca currents that were decreased in diabetic mice were partially recovered in rotenone‐treated diabetic mice ( P < 0.05 vs untreated diabetic group). 4 The posterior cerebral artery from diabetic mice had a significantly higher myogenic tone than the control group, but this impaired contraction was partially reversed in the rotenone‐treated diabetic group ( P < 0.05 vs untreated diabetic group). 5 The H 2 O 2 concentration was significantly increased in cerebral arteries from diabetic mice compared with control. This increase in H 2 O 2 was significantly blunted by rotenone treatment. 6 In conclusion, rotenone partially reverses the decreased macroscopic BK Ca currents in STZ‐induced Type 1 diabetic mice and this reversal of BK Ca currents may be related to the inhibitory effects of rotenone on H 2 O 2 production. Reactive oxygen species, particularly H 2 O 2 , are important regulators of BK Ca channels and myogenic tone in diabetic cerebral artery.